Head and neck cancers strike 41,000 new persons each year in the U.S. Survival is only 50% and treatments leave most patients with functional deficits and disfiguration. Improved treatments are desperately needed. In preliminary studies, we achieved high levels of gold specifically in tumors after intravenous injection of Nanogold, a gold nanoparticle. Because high-Z elements absorb X-rays and increase local dose, we found irradiation of mice with tumors resulted in dramatic tumor regressions and long term survivals (86%, >lyr) compared with mice irradiated without Nanogold (20%). Here we propose to investigate Nanogold-enhanced radiotherapy in a squamous cell carcinoma murine model using tomographic and fractionated irradiation and develop targeted gold agents to find their potential to improve treatment of head and neck cancers. Nanogold will be conjugated to epidermal growth factor (EGF) since other EGF conjugates have shown excellent targeting to head and neck tumors. Pharmacokinetics will be measured using a microCT instrument to map gold biodistribution and uptake in vivo over time in the tumor and other tissues. SCCVII squamous cell carcinoma tumors will be implanted in the neck of mice and the head and neck region irradiated. End points relevant to head and neck irradiation, mucositis, salivary gland damage, and fibrosis will be evaluated. The TCD50, ED50 and Therapeutic Index with and without gold will be measured and compared to other treatments. Synchrotron generated X-rays with a mean energy of 120 keV will be used, optimal for gold enhancement. If treatments show significant promise, Philips Medical Systems, a major CT manufacturer, has indicated that they could provide CT retrofits or instruments to implement Nanogold-enhanced tomographic radiotherapy, thus making the method potentially widely available for clinical use.